As of this report, the NIAAA Repository/Screening Database includes phenotype and/or genomic data on more than 2300 individuals. Phenotype data include psychiatric diagnoses, a number of alcohol-related assessments and measures including lifetime and recent consumption and alcohol response phenotypes, personality and impulsivity measures, depression and anxiety symptoms, current and early life stress and trauma, aggression, suicidality, smoking, IQ, sleep quality, pain, and overall quality of life. Laboratory/biochemical measures are also available. Genomic data include large-scale single nucleotide polymorphism (SNP) genotyping performed using Illumina arrays via a partnership between the Clinical Core Laboratory of the OCD, and the Laboratory of Neurogenetics (NIAAA). All NIAAA PI's are encouraged to submit data requests in order to conduct research projects and analyses using the shared NIAAA Repository/Screening Database. Projects are logged and the status is tracked from initial request to manuscript publication. In addition, Human and Genomic data are shared via BTRIS and other mechanisms, including collaboration with NIH-supported consortia (PGC Alcoholism, ENIGMA) to ensure data sharing. Development of standardized assessments of alcohol responses (Mini alcohol screening exam -MASE), neurobiological changes during the addiction cycle (Addictions Neuroclinical assessment -ANA) and measures of addiction are proceeding via the natural history protocol and also via neuroimaging studies in the OCD Neuroimaging core (PI, Reza Momenan). Using the clinical database, factor and pathway analyses are being performed to identify factors, and clinical subgroups within patients with AUD who are heterogeneous both etiologically and in terms of clinical outcome. I. Projects resulting in manuscripts published within the past year The development of the Addictions Neuroclinical assessment has resulted in two publications. A comparison of characteristics and clinical outcomes in alcoholic inpatients with and without comorbid posttraumatic stress disorder (PTSD) Effects of fatty acid amide hydrolase (FAAH) genetic variation and alcohol-related outcomes and severity of alcohol dependence Investigating the role of the Leu72Met polymorphism of the prepro-ghrelin gene in alcohol dependence and alcohol-related behaviors Effects of sex, drinking history, and fatty acids on liver injury in heavy drinking alcohol-dependent inpatients FAAH genetic variation, anxiety, and brain response to negative stimuli alcohol dependent inpatients with comorbid PTSD Effect of genetic variation in the vesicular monoamine transporter 1 (VMAT1/SLC18A1) gene on alcohol withdrawal severity Corticotropin releasing factor binding protein (CRF-BP) genetic variation in alcoholism and alcohol-related phenotypes A comparison of characteristics and clinical outcomes in treatment-seeking versus non treatment-seeking alcohol dependent individuals Hepatic, lipid and genetic factors associated with obesity and their association with alcohol dependence Assessment of the validity of the Montgomery-Asberg Depression Rating Scale (MADRS) in identifying depression diagnoses in alcohol dependent inpatients II. Projects resulting in manuscript submissions, or publications in press, within the past year There were three manuscripts submitted and/or accepted for publication in peer-reviewed journals during the reporting year that were the result of research projects using the NIAAA Repository/Screening Database. These projects include: The role of genetic variation and dysregulation of proprotein convertase subtilisin/kexin 9 (PCSK9) in alcoholism and alcohol-related phenotypes Impulsivity mediates the relationship of adult attention deficit hyperactivity symptoms and alcohol dependence severity Investigating the role of the cluster of differentiation 38 (CD38) rs3796863 polymorphism in alcohol and monetary reward: possible involvement of dopamine signaling III. Projects with manuscripts in preparation There are six projects with manuscripts in preparation: Early life stress is associated with suicidality in alcoholic inpatients Effects of the orexin (hypocretin) receptor 2 gene polymorphism Val308Ile on severity of alcohol dependence and stress response in alcohol-dependent subjects. Association analysis of genetic variation in GATA Binding Protein 4 (GATA4) and alcohol use disorder Genetics and epigenetics of the dopamine transporter (DAT) in alcohol use disorder Obsessive craving as a predictor of suicidal ideation in alcohol dependent inpatients Assessment of Addictions Neuroclinical Assessment (ANA) domains using measures from the current NIAAA screening protocol IV. Ongoing projects still in progress There are four projects still ongoing from the previous year: GABA (GABBR1 and GABBR2) and GABA transporter 1 (GAT1) genetic variation in alcoholism and alcohol-related phenotypes. Data analyses are ongoing. Association between DCC netrin 1 receptor (DCC) and synuclein alpha (SNCA) genes and measures of impulsive behavior in alcoholic patients and controls. Data analyses are ongoing. Genetic variation in serum/glucocorticoid regulated kinase 1 (SGK1) and associated clinical phenotypes in alcohol use disorder. Data analyses are ongoing. Exome sequencing of alcoholic inpatients with low and high withdrawal. Sequencing is ongoing. V. New projects initiated within the past year There were eleven new research projects initiated during the reporting year: Genetics of vasopressin and vasopressin receptors in alcoholism. Data analyses are ongoing. The role of C-Reactive protein in alcohol use disorder. Data analyses are ongoing. Free peptide and receptor genotype of the appetitive hormones, leptin and amylin, and their association with alcohol-related phenotypes. Data analyses are ongoing. Calcium as a modulator of alcohol use disorder and the response to Acamprosate. Data analyses are ongoing. GWAS and pathway-informed analysis of externalizing behaviors. Data analyses are ongoing. Sex differences in glucose and insulin signaling and their association with trait aggression in individuals with and without alcohol use disorder. Data analyses are ongoing. Comparison of personality measures between individuals with alcohol dependence, regular alcohol use and no alcohol use. Data analyses are ongoing. Evaluation of the relationships between craving and alcohol use disorder, sleep, pain, social support and co morbid axis-1 diagnosis. Data analyses are ongoing. Decision making differences and alcohol use severity: the relationship between delay discounting and risky drinking. Data analyses are ongoing. The role of EF-hand domain family member D2 (EFHD2) in alcohol use disorder relevance for individuals exhibiting sensation-seeking behavior. Data analyses are ongoing. Analysis of protein kinase, cGMP-dependent, type I (PRKG1) variation in stress experience and alcohol use disorder. Data analyses are ongoing. VI. Other Progress During the reporting year, a collaboration was esablished with the Psychiatric Genetics Consortium (PGC), and data from the NIAAA Repository/Screening Database including large-scale genomic data and alcohol dependence diagnosis were shared with the consortium.